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Animal studies reveal new route to treating heart disease
Date:5/2/2011

Scientists at Johns Hopkins have shown in laboratory experiments in mice that blocking the action of a signaling protein deep inside the heart's muscle cells blunts the most serious ill effects of high blood pressure on the heart. These include heart muscle enlargement, scar tissue formation and loss of blood vessel growth.

Specifically, the Johns Hopkins team found that their intervention halted transforming growth factor beta (TGF-beta) secretion at a precise location called cell receptor type 2 in cardiac muscle cells. Blocking its action in this cell type forestalled pathways for hypertrophy, fibrosis, and angiogenesis by stopping the unbridled TGF-beta signaling, which is typically observed in heart failure, in all other non-muscle types of cells in blood vessels and fibrous tissue. However, blocking TGF-beta signaling in non-muscle cells did not stop disease progression.

In several dozen different experiments, using genetically altered mice or chemicals to selectively block different TGF-beta pathways, researchers were able to pinpoint where the signaling protein had its greatest impact on heart function and determine how its unimpeded activity promoted heart disease.

"Now that we know about the pivotal and specific bad roles played by TGF-beta in a common form of heart disease, we can try to mimic our lab experiments to develop cell-specific drug therapies that stop the chain reactions in the heart muscle at the TGF-beta type 2 cell receptor location," says senior study investigator and cardiologist, David Kass, M.D. Kass is a professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute.

The Kass team study, to be published in the June edition of the Journal of Clinical Investigation, is believed to show the first evidence of how TGF-beta is stimulated differently by various cell types in the heart and which resulting pathways promote heart failure, the most common k
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Contact: David March
dmarch1@jhmi.edu
410-955-1534
Johns Hopkins Medical Institutions
Source:Eurekalert

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